2,3,7,8 Tetrachlorodibenzo-p-dioxin (TCDD) and other chlorinated dibenzo-p-dioxins and dibenzofurans are contaminants formed during the commercial synthesis of a number of chlorinated phenolic products. The extensive use of these chlorinated phenolic or benzene products (2,4,5 trichlorophenoxyacetic acid, a herbicide; pentachlorophenol, a bacteriostat; and the polychlorbiphenyls, a heat exchange fluid and plasticizer) has resulted in widespread environmental pollution with the polychlorinated dibenzo-p-dioxins and dibenzofurans. TCDD is the most potent small molecule toxin and teratogen known, and because of its toxicity, chemical unreactivity and prolonged biological storage poses a potentially serious health hazard. TCDD appears to be a cellular poison producing gradual hepatic necrosis and death. Preliminary investigations are presented on the biochemical effects of TCDD on the liver which are dose related and produced only by the dioxins known to be toxic. TCDD is a potent inducer of alpha-aminolevulinic acid synthetase and is the likely cause of porphyria observed in workers in a herbicide plant. TCDD is a potent inducer of aryl hydrocarbon hydroxylase, being 3 x 10 to the 4th power more potent than polycyclic hydrocarbons. It is proposed that the mechanism of toxicity of TCDD and related compounds arises from its metabolism to a chemically reactive intermediate, catalyzed by aryl hydrocarbon hydroxylase. We propose to study the metabolism, storage, distribution and mechanism of toxicity of these compounds. These data should permit some inferences about the hazard of low-level chronic exposure to the dioxins. In addition, because of its remarkable potency in inducing drug metabolism, we plan to investigate the "induction receptor binding site" and early events in enzyme induction produced by TCDD.